Double cyclization towards nucleophiles

In agreement with these analyses, it was found that conqiound S was unreactive toward base-catalyzed cyclization to 6, even though the double bond would be expected to be reactive toward nucleophilic conjugate addition. On the other hand the acetylene 7 is readily cyclized to 8 ... 

In the presence of molecular iodine, the C-C double bond of allylamines and homoallylamines can be activated towards nucleophilic attack by carbamate anion. Accordingly, iodoalkyloxazolidinones and iodoalkyloxazinanones have been prepared under mild conditions (ambient temperature, atmospheric C02 pressure) by the reaction of allylamines and homoallylamines with C02 and iodine via intramolecular cyclization [88],... 

In order to predict the stereochemical outcome of a cyclization, some rules have been proposed based on a model for the attack of an electrophile, under kinetic control, to an alkene containing an internal nucleophile. The selectivity is determined by the relative affinity of the diastereotopic face of the double bond towards a proton syn to H in an OH-in-plane-conformer, or syn to OH in a H-in-plane-conformer, and the cyclization involves a probable intramolecular attack on a 7i-compIex. In fact, when a hydroxy or an alkoxy group is present, the electrophile preferentially attacks the OH-in-plane-conformer from the face of the double bond syn to the allylic hydrogen 22. Thus, starting from terminal double bonds, the ci.v-diastereomer is prevalent in the reaction mixture. 

Unsaturated amides are easily converted to imidates by 0-alky la ting reagents such as trimethyl-oxonium telrafluoroborate or trimethylsilyl triflate. Nucleophilic attack by the thus formed imino group on an halonium ion followed by hydrolysis gives a lactam. Thus an unsaturated dimethyl imidate was treated with bromine in dichloromethane at 0 °C and cyclized with total regio- and stereoselectivity to give 1, since the tertiary cation forces the cyclization towards the formation of a six-membered ring. The trans addition to the double bond was shown by successive conversion to a m-aziridine 2126. 

While the notion that the alkoxides derived from aliphatic alcohols are poor nucleophiles toward 7r-allylmetal complexes has prevailed over the years, much progress made in the recent past has rendered the transition metal-catalyzed allylic alkylation a powerful method for the O-allylation of aliphatic alcohols. In particular, owing to the facility of five- and six-membered ring formation, this process has found extensive utility in the synthesis of tetrahydrofurans (THFs) (Equation (29))150-156 and tetrahydropyrans (THPs).157-159 Of note was the simultaneous formation of two THP rings with high diastereoselectivity via a Pd-catalyzed double allylic etherification using 35 in a bidirectional synthetic approach to halichondrin B (Equation (30)).157 The related ligand 36 was used in the enantioselective cyclization of a Baylis-Hillman adduct with a primary alcohol (Equation (31)).159... 

Towards electrophiles, the reactivity of vinylsilanes is similar to that of the corresponding alkene. However, incorporating a silicon substituent at the vinylic carbon of a ir-nucleophile markedly affects the cyclization outcome. Specifically, iminium ion-vinylsilane cyclizations occur cleanly to substitute, preferentially with retention of double-bond configuration, the iminium ion carbon for the silyl substituent. Both endocyclic and exocyclic modes of intramolecular electrophilic substitution have been demonstrated (Scheme 35). 

Other aspects of nucleophilicity toward vinyl cations are the site of capture of ambident ions and the easy intramolecular cyclization by o-methoxy and o-thiomethyl substituents on a P ring. The extensively studied P-aryl rearrangement across the double bond could be regarded as intramolecular substitution by the aryl ring, and data are available on the relative rate of rearrangement and capture by the solvent (69, 70). These topics are not discussed here for lack of space but should be addressed in a more complete discussion of the nucleophilicity. 

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